Clinical Accelerator, a full-service contract research organization, is pleased to announce that it has entered into a collaboration with Archivel Farma, for conducting a phase IIa clinical trial for their therapeutic vaccine RUTI® against multi-drug Resistant tuberculosis. The double-blind, randomized and placebo-controlled trial will take place at several specialist tuberculosis sites in the Ukraine alongside with Groningen University Medical Centre in the Netherlands, and will be testing the vaccine’s safety and immunogenicity.

The RUTI® vaccine stimulates host immune effectors directed at bacilli that persist under antibiotic therapy of tuberculosis. It works in tangent with standard antibiotic treatment, improving the efficacy of the standard antibiotic treatment and reducing the chance of recurrence. Clinical safety and immunogenicity has already been proven in healthy volunteers and in individuals with latent tuberculosis infection, both HIV +/ in phase I and II studies. The purpose of the current study is to show that it is safe in patients with multidrug-resistant (MDR-) TB at two different time points of vaccination.

With this study, Archivel Farma aims to evaluate the safety and immunogenicity and to explore the efficacy as the reduction of bacillary load in the sputum of the novel anti-TB vaccine RUTI®, and collect data that could potentially assist in pin-pointing the optimal time to administer RUTI®.

About Clinical Accelerator

Clinical Accelerator is an independent clinical trial management organisation operating principally in Central and Eastern Europe. The organisation offers a broad range of clinical trial services together with dedicated patient enrolment support to worldwide clients in the pharmaceutical, biotechnological, nutraceutical and medical device industries. Clinical Accelerator’s model of operation is designed to achieve significant cost savings for its clients and to guarantee compact timelines for patient enrolment with a firm focus on the quality of clinical trial data.

About Archivel Farma

Archivel Farma is an R&D biotech company that develops immunotherapeutic agents to tackle unmet medical needs. The company was founded in 2005 and has ever since been committed to fighting tuberculosis which affects 10 million people every year.

The Director of Clinical Accelerator, Nik Nikitin MD, PhD says, there are significant unmet medical needs in the management of multi-drug resistant tuberculosis (MDR-TB). A large proportion of MDR-TB cases occur in Central and Eastern Europe where Clinical Accelerator runs its clinical studies. The novel anti-TB vaccine RUTI, which is being developed by Archivel Farma can make an important contribution to the fight against MDR-TB in our region of operation and globally. On behalf of Clinical Accelerator, we will be making every effort to make sure that the study is implemented within compact timelines and with high quality.

Below, we are re-publishing with permission the press-release issued by the Heart Institute on the 28th of September 2018

“Thanks to the efforts of the study team from the Heart Institute, we have conducted the first worldwide implantation of the VisONE system that we have developed, and we are going to demonstrate the benefits of the asymptomatic diaphragmatic stimulation (ADS) in heart failure patients and reduced ejection fraction”, – Peter Bauer, President and CEO of VisCardia Inc. in his report at the XIX Ukrainian National Congress of Cardiology (26-28th of September 2018, Kyiv).

On July 25, 2018, the first world-wide implantation of VisONE®, a medical developer VisCardia Inc., was carried out at the Kyiv Institute of Heart in clinical conditions. Thus, the start of an important Pilot Study on the VisONE Heart Failure Study in Ukraine was launched on the use of devices for the treatment of patients with heart failure.

Director General of the Heart Institute – Borys Todurov (left) and President and CEO of VisCardia Inc. – Peter Bauer.

The implantation was held under the control of the Director of Heart Institute, Associate Member of the National Academy of Medical Sciences (NAMN) of Ukraine, Professor Borys Todurov and the Study Principal Investigator Vitaliy Demyanchuk, MD, PhD.

In the 53-year-old patient with a left ventricular ejection fraction lowered to 17%, symptomatic heart failure was observed, despite the optimally chosen regimen of drug therapy. The lack of proper treatment outcome on the one hand and alternative therapies on the other, dictated the use of the VisONE® system.

Surgeon Oleksandr Plegutsa, MD, PhD who performed laparoscopic implantation, emphasized: “The practicality and feasibility of this new and minimally invasive approach reduces the time of the procedure, which is especially important for patients with heart failure. This allows them to recover more quickly than previously applied medical practices.” The implanted system is equipped with an electrical pulse generator, which provides asymptomatic diaphragm stimulation (ADS) to improve the function of the heart. The preclinical studies have shown that ADS improves acute hemodynamic parameters and left ventricular ejection fraction, remaining asymptomatic and devoid of side effects by the technique.

“We are very pleased that this innovative therapy approach will help patients who were previously almost doomed. Our Institute will actively and scrupulously study the effect of this method on heart failure”, – Professor Todurov, Director of the Heart Institute.

Additionally, data from the Evitar™ proof-of-concept randomized clinical trial was recently accepted for presentation at 47th Annual Global Congress of AAGL (American Association of Gynecologic Laparoscopists) scheduled for November 2018.

“Post-surgical adhesions are broadly recognized as the single greatest cause of surgical complications. Moreover, they have evaded effective intervention, until now” comments Sanj Singh, CEO of Temple. “These mechanism-of-action and randomized clinical trial data speak to the underlying biology driving surgical adhesions. We are pleased to note the publication’s acceptance in Reproductive Sciences, a high-impact, peer-reviewed journal. This publication and the forthcoming AAGL presentation further support the Evitar™ value proposition. Adhesion prevention is only the beginning. However, it provides a relevant model to further the study of both fibrosis and cancer pathophysiology. Temple is leveraging these insights to further its pipeline of first-in-class therapeutics for the management of adhesions, endometriosis and ovarian cancer.”

About Temple Therapeutics BV

Temple Therapeutics BV is a privately held Dutch based clinical stage development therapeutic drug company, developing first in class and best in class therapeutics to treat acute/chronic fibrosis and cancer. With novel targets linked by a common underlying biology, Temple’s platform has yielded three promising drug candidates to treat post-operative adhesions, endometriosis and ovarian cancer.

About Reproductive Sciences

Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology making it one of the highest ranked and cited journals. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.

Clinical Accelerator, a full-service contract research organization, is pleased to announce that it has entered into a collaboration with Oncolix, for conducting clinical studies for its analogue protein, Prolanta, to treat ovarian cancer. The trials will be conducted in the US as well as sites A and B in the Ukraine.

Ovarian Cancer is one of the leading causes of cancer-related death in women and gynecologic death[1]. 80-90% of patients initially respond to chemotherapy but of those, only 10-30% have long-term survival since the majority relapse. Currently, cytotoxic drugs (chemotherapy) are the only forms of therapy that are available, but as shown, they are not particularly efficacious. Clearly there is a great need for new forms of treatment.

Prolanta is a prolactin receptor antagonist with a single amino acid mutation. This mutation would allow Prolanta to interfere with the binding of two normal prolactin receptors, which would usually cause cancer cell proliferation and also resistance to chemotherapy. It does so through its ability to bind to one prolactin receptor but not the other, blocking prolactin from initiating growth pathways such as the Jak2/STAT pathway. There is significant evidence that this mutated form of prolactin also induces autophagy in ovarian cancer cells.

The purpose of this Phase I study is to evaluate the safety, tolerability and pharmacokinetic parameters of Prolanta monotherapy in patients with recurrent or persistent ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.[2] Three dosing levels will also be examined to establish the recommended Phase II dose.

About Clinical Accelerator

Clinical Accelerator is an independent clinical trial management organisation operating principally in Central and Eastern Europe. The organisation offers a broad range of clinical trial services together with dedicated patient enrolment support to worldwide clients in the pharmaceutical, biotechnological, nutraceutical and medical device industries. Clinical Accelerator’s model of operation is designed to achieve significant cost savings for its clients and to guarantee compact timelines for patient enrolment with a firm focus on the quality of clinical trial data.

About Oncolix

Oncolix is a Houston, Texas-based, clinical-stage bio-pharmaceutical company dedicated to the development of Prolanta for the treatment of breast, ovarian and other cancers. Oncolix has received approval by the FDA to designate Prolanta as an Orphan Drug for ovarian cancer due to the unmet medical needs.

Below, we are re-publishing with permission the press-release issued by VisCardia Inc. on the 1st of August 2018

PORTLAND, Ore.–VisCardia Inc., a privately held medical device developer, announced today the first implant of the VisONE® implantable system for heart failure, and the commencement of its VisONE Heart Failure pilot study in Ukraine*.

The VisONE implantable system delivers VisCardia’s proprietary Asymptomatic Diaphragmatic Stimulation (ADS) therapy to improve cardiac function. By electrically stimulating the diaphragm in an asymptomatic manner, transient intrathoracic pressures gaited to cardiac activity are applied against the cardiac walls, improving both cardiac filling and output. “Our preclinical and early feasibility studies demonstrated ADS improves acute hemodynamic parameters and chronic left ventricular ejection fraction, while remaining asymptomatic and with no adverse effects. With our newly developed implantable VisONE system, we intend to demonstrate ADS benefits the majority of moderate heart failure patients with reduced ejection fraction,” said Peter Bauer, VisCardia’s President and CEO.

“During this 12-month pilot study, we are optimistic VisONE will deliver comparable benefits as those observed during our ADS feasibility studies,” said Paul Erne, M.D., Professor Emeritus of Cardiology at the University Hospital of Basel and former Head of Cardiology at the Kantonsspital of Lucerne, Switzerland.

The implant took place at the Heart Institute, Kyiv, Ukraine, under the leadership of Institute Director Professor Borys Todurov, M.D., Ph.D., and Principal Investigator Dr. Vitaliy Demyanchuk, M.D., Ph.D. The patient, a 53-year-old male with a reduced ejection fraction of 17%, remained in symptomatic heart failure despite an optimally titrated medical regimen, and had no alternative treatment options. General Surgeon Dr. Oleksandr Plehutsa, M.D., Ph.D., who performed the laparoscopic implant, stated, “The practicality and expediency of this novel and minimally invasive approach reduces critical anesthesia times for this delicate heart failure population, enabling a quicker recovery versus established medical device therapies.” Furthermore, Dr. Todurov added, “We are excited at the potential of this therapy to address a significant gap in clinical care. Our center will be actively and methodically studying its impact on heart failure.”

Echocardiographic data will be analyzed at the University Hospital of Zurich under the direction of Professor Felix Tanner, M.D., with statistical analysis performed at the Robertson Centre for Biostatistics in Glasgow under the guidance of Professor John Cleland, M.D. Michael Mirro, M.D., VisCardia’s Director of Medical Affairs, commented, “Given the promising evidence to date, it is exciting to see two recognized groups engaged in studying this new therapy with the proper clinical rigor of a multicenter study used by prominent heart centers.”

About VisONE® ADS Therapy

ADS therapy utilizes a medical device with electrodes, implanted using a minimally invasive laparoscopic surgical procedure, to deliver electrical pulses to precise areas of the diaphragm. The therapy is non-invasively adjusted and programmed using an external programmer to improve hemodynamic benefit and eliminate undesired stimulatory side effects.

About VisCardia

VisCardia, based in Portland, OR, is developing a novel implantable device therapy for treating heart failure, a condition that afflicts 10 million patients in the U.S. and Europe. To learn more about VisCardia, visit: http://www.viscardia.com.

Clinical Accelerator is a clinical CRO with a special focus on Central and Eastern Europe currently operating in 11 countries of that region: Bulgaria, Estonia, Georgia, Hungary, Latvia, Lithuania, Moldova, Poland, Romania, Russian Federation, and the Ukraine (listed alphabetically).

The quality of clinical trial data originating in our countries of operation and its acceptance by the FDA is a frequent topic of discussion with Clinical Accelerator’s partners and clients. In this post we present an analysis of the latest data made available by FDA.

We know first-hand that the clinical trials we conduct in Central and Eastern European countries produce data meeting all the standards set by regulatory agencies around the world. However, we’re also aware of the misconception that clinical research carried out in this region does not conform to the standards of data quality and Good Clinical Practice seen in Western Europe and Northern America.

How do countries in Central and Eastern Europe compare with the rest of the world?

Today, clinical trials operate on a global stage. According to the latest report of Office of Inspector General, US Department of Health and Human Services, more than 80% of the US FDA approved marketing applications now contain data acquired outside the US. Our countries of operation are well established contributors to this.

According to clinicaltrials.gov, for example, there are 5535 registered trials in Poland, 4080 in Russia, 3454 in Hungary and 2210 in Romania. It is unsurprising then, that the FDA is increasingly interested in foreign sites involved in conducting clinical trials.

Clinical trials sites

Central and Eastern Europe (CEE) is a major contributor of investigative sites to global clinical trials, currently providing 11% of all sites worldwide.

The region is especially attractive to sponsors thanks to the excellent levels of patient recruitment that are characteristic of CEE countries. The average reported recruitment rate in CEE is of 10.3 patients per site compared to 7.5 per site in Western Europe.

In Central and Eastern Europe, our countries of operation are amongst some of the highest ranking for the number of sites participating in industry-sponsored clinical trials: Poland (4320), Czech Republic (2201), Hungary (2115), Ukraine (2002), Romania (1618) and Bulgaria (1004). The number of sites participating in clinical trials in the Baltic countries stands at 386 for Lithuania, 320 for Estonia and 319 for Latvia.

By the number of sites participating in FDA-overseen clinical trials, Russia is currently ranked No. 2 in Europe (after Germany) and No. 4 in the world (after US, Canada and Germany) with 3340 sites. The Ukraine is also climbing up the list fast, currently being No. 11 in Europe and No. 19 in the world with 1141 sites. For comparison, there are 2831 sites overseen by FDA in the UK and 1866 sites in India.

FDA inspections

It is unsurprising that facilities operating in CEE have attracted scrutiny from the FDA, given the high number of clinical trials being operated in the region. In the last decade, 300 FDA inspections of Bioresearch Monitoring have been carried out in our countries of operation in CEE. The majority of inspections have been conducted in Poland (109)- pushing them up in ranking above Canada (88) and Germany (96). Other contributors to the number of FDA inspections in CEE are Hungary (34), and Romania (31), Russia (67), Ukraine (29), Latvia (4), Lithuania (6), Estonia (3) and Georgia (17).

This reflects the growing status of CEE countries as leading global locations to conduct clinical trials.

FDA inspection outcomes

The results of these inspections have proved to be somewhat unexpected for some critics of the so-called “emerging locations” in CEE.

Based on the most recent statistics available, our own analysis of FDA inspections outcomes based on the top 5 most inspected countries shows that our countries of operation such as Poland and Russia outperform Canada, Germany, and the UK. In the last decade, the percentage of NAI inspections (no objectionable conditions or practices were found during the inspection) was higher in Georgia (100%), Romania (74%), Ukraine (72%), Russia (66.3%), Hungary (65%) and Poland (58.5%), compared with Canada (54.4%), Germany (47.8%), and the UK (42.1%). For inspections where action was indicated, the average number of deficiency codes in Russia (1.24) and Poland (1.44) was lower than in Canada (1.67), the UK (1.95) and Germany (1.89).

Our own analysis is supported by previously published studies. A 2010 analysis of FDA data showed that Eastern Europe (with 264 US FDA inspections) has the best overall results worldwide, with only 3.3% of its site inspections having three or more deficiencies, 0.85% in Russia and 0% in the Ukraine, compared with 20.2% in Western Europe after 506 inspections.

A more recent analysis comparing CEE with Western Europe and the USA gives an equally positive account. Clinical trials in CEE are more likely to result in NAI (No Action Indicated) outcomes of FDA inspections. In our countries of operation 73% of inspections of Bioresearch Monitoring resulted in NAI in the last decade. In comparison, only 56% of inspections resulted in NAI in the USA. The average number of deficiencies per inspection is lower in CEE than in Western Europe and the USA, at 0.99, 1.99, and 1.59, respectively. Finally, the rate of inspections for which objectionable conditions were found, warranting regulatory and/or administrative sanctions, were lower in CEE (1%), than in the USA (2%) and Western Europe (4.5%).

Figure 1: FDA inspections of Bioresearch Monitoring:

Country

Total

NAI

VAI

OAI

Estonia

3

1

2

0

Georgia

17

17

0

0

Hungary

34

22

12

0

Latvia

4

2

2

0

Lithuania

6

2

4

0

Poland

109

79

30

0

Romania

31

23

8

0

Russia

67

52

15

0

Ukraine

29

21

8

0

UK

45

20

24

1

Canada

88

64

23

1

Germany

96

62

34

0

US

4,095

2,299

1,593

203

Australia

14

9

5

0

Repeated analysis of FDA inspection data has shown what we’ve always believed at Clinical Accelerator – that clinical trials conducted in CEE are of an equally high standard to those carried out in Western Europe and Northern America. We believe that all the extensive evidence of the quality of clinical trial data in CEE acquired as a result of FDA inspections over the last 5 years should be very reassuring for international companies considering placing their clinical trials in these regions.

Due to the fast growing contribution of these countries to global clinical trials and increasing interest of FDA, we expect more evidence of the quality of clinical trial data will emerge.

We will continue to monitor the data coming from FDA inspections and will re-visit this topic again in one of our future posts.

A higher proportion of patients with at least one-point improvement in fibrosis score without worsening of NASH was demonstrated in Aramchol 600mg vs. placebo, in the 52-week biopsy, a regulatory approvable endpoint.

Statistically significant reductions in ALT and AST were demonstrated in Aramchol 400mg and 600mg vs. placebo.